Pediatric Transplants Find Growing Success New Drugs, Novel Treatments Hold Promise for Higher Survival Rates by Kurt Samson Last Memorial Day, pediatric transplant surgeons at the Riley Hospital for Children in Indianapolis gave 8-month-old Nolan King a new heart. Diagnosed in infancy with congestive heart failure, the operation was a matter of life and death. The procedure was a success, and by July, Nolan was photographed grinning at his parents from his swing, looking healthier than the Gerber baby. Thanks to newer anti-rejection drugs and growing expertise in pediatric transplant techniques at U.S. hospitals, Nolan is just one of thousands of young children who have received hearts, kidneys, livers, lungs and other transplants in recent years. Although pediatric transplants represent only a fraction of total procedures, some experts expect survival rates for children to eclipse those for adults in the coming years. In addition, today’s experimental pediatric transplant techniques will become tomorrow’s standard of care, further improving long-term survival. According to the United Network for Organ Sharing (UNOS), 20,704 pediatric transplants have been performed since 1988. This includes 9,167 kidneys, 7,144 livers, 57 pancreatic transplants, 18 kidney-pancreas procedures, 3,315 heart transplants, 519 lung transplants, 130 heart-lung transplants, and 354 intestinal transplants. Although the annual number of pediatric transplants has edged up only slightly in the past five years—it currently stands at around 1,700—heart, lung, liver and heart-lung transplants have increased, as have survival rates for kidney and liver transplants. The wait for transplantable organs is significantly shorter for children, largely because UNOS allocation policies require that they be given preference when organs become available. For example, the wait for a kidney averages 300 days for children, compared to 891 days for adults. Pediatric liver recipients wait 237 days, compared to 392 days for adults. And pediatric heart registrants wait just 51 days, whereas adults wait an average of 214 days. "Most kidney transplant patients are between the ages of 50 and 65 years, but pediatric survival rates are much higher because older patients tend to die sooner from other diseases," said William Harmon, director of the Nephrology Division at Children’s Hospital Boston and an associate professor at Harvard Medical School. "Organ graft rejection is the biggest risk for pediatric patients, but because we have newer drugs and children tend to have healthier immune systems, their long-term survival rates are improving," Harmon said. Success rates for pediatric kidney transplants are also higher because family members are more willing to donate an organ, added Harmon, who is also chairman of public policy for the American Society of Transplantation. For adults, only 15 percent of kidneys comes from living donors, while the rate for children in recent years has increased to about 50 percent. A living donor transplant is often less complicated. There is less chance of rejection, and there is immediate function of the organ, he said. New experimental procedures are also expected to decrease waiting times and increase survival for pediatric liver transplant patients. Some transplant centers already use split liver transplants—where part of a donated liver is transplanted into a child while the rest goes to an adult patient. Mount Sinai Hospital in New York, home to one of the largest liver and organ transplant centers in the country, consistently performs split-liver operations, and its pediatric program boasts a 92 percent one-year survival rate. Remarkably, because of a liver’s unique regenerative properties, this small part of the liver functions like a healthy organ as the child grows. Dr. Kenneth Cox, director of the Pediatric Gastroenterology, Hepatology and Nutrition program at the Lucile Packard Children’s Hospital at Stanford University Medical Center, said researchers there are exploring cross-blood typing for pediatric transplant patients. "We’ve discovered that unlike adults, younger children can tolerate transplanted tissue and organs from donors of different blood types." The Stanford doctors are also investigating why some children accept organ transplants without the need for immunosuppressive drugs, unlike adults, while others can be weaned off the drugs after a period of time. Cox said one finding that puzzles the researchers is that many of their pediatric patients who become infected with Epstein-Barr virus (mononucleosis) after receiving a liver transplant are able to stop taking immunosuppressive drugs. "We have a lot of kids that don’t need immunosuppressive drugs. What we want to do is understand why," Cox said. "How can we induce this tolerance? That’s what we’re studying now." Elsewhere at Children’s Hospital Boston, Dr. Anthony Atala, a pediatric surgeon, is using an emerging technology called tissue engineering to "grow" artificial organs. His first effort is an artificial bladder that has worked in larger mammals, and the first human trials are expected later this year. Atala first extracts bladder cells from the patient, then places them in a special growth culture where they quickly multiply. Once enough cells have been grown, they are affixed to muscle tissue surrounding a biodegradable polymer matrix shaped like a normal bladder. Once implanted, the matrix dissolves over a period of about three months and the new bladder functions like a normal organ. Atala said the same process could be used to grow other organs. Already he has developed small experimental kidneys that filter waste and excrete urine. He and other researchers hope their efforts will alleviate or even eliminate the wait for transplantable organs and other tissues in the years to come. "What we learned in creating the artificial bladder was the process, and the correct ‘soup’ in which to grow the cells," he said. "Since then we have grown heart and tracheal tissue, in addition to cartilage, muscle, bone, blood vessels and nerves. These are the basic elements. With a polymer scaffold, these are [what] you need to build organs." At the Pediatric Bone Marrow Transplant Program at the University of California, San Francisco, researchers are transplanting stem cells harvested from bone marrow to treat a wide range of childhood diseases. The process is effective against certain cancers, severe combined immunodeficiency disease (SCID), aplastic anemia, sickle cell anemia and thalassemia, a metabolic disease, according to program director Dr. Morton Cowan. To date, the center has performed more than 400 transplants. For various cancers, the success rate is between 60 percent and 70 percent, but as high as 90 percent for some inherited blood diseases. But an even more ambitious program is under way at the center: Cowan and his team have begun transplanting marrow stem cells in utero. "We have long been interested in the fetus as a recipient of bone marrow stem cells because early in gestation the fetus does not reject donor cells," he explained. The center transplants stem cells from a parent into fetuses diagnosed with thalassemia or SCID. "This novel approach will someday permit infants, whose diseases are diagnosed while still in the womb, to be born with no evidence of their disease," Cowan said. The center has performed three in utero transplants, out of about 40 worldwide. For now, however, the current UNOS allocation system helps sick children get donated organs as soon as possible, said Joel Newman, a spokesman for the organization. He noted that the system makes no distinction between U.S. children who are awaiting organs and children from foreign countries that come to the United States for transplants. Although their number is relatively small, non-resident pediatric patients are entitled to the same special treatment that U.S. children receive; however, the allocation system requires that no more than 5 percent of transplants at any U.S. hospital or transplant center be for non-resident foreign children, he said. As 8-month-old Nolan King received his new heart, 11-year-old Dimitris Attiti, a boy from Greece, was recovering from a kidney transplant performed by surgeons at the University of Maryland Medical Center in Baltimore. Because neither parent matched his blood type, Dimitris’s healthy 58-year-old grandfather volunteered. Transplanting a kidney from an adult to a child is often very successful because children’s bodies adapt to an adult-size kidney, said Dr. Alan Farney, who performed the transplant. The center has the largest kidney transplant program in the United States, and surgeons there have performed more laparoscopic kidney removal procedures from living donors than any other hospital in the world, Farney said. The laparoscope, a narrow, flexible tube equipped with a miniature camera, allows surgeons to remove a kidney through a two-and-a-half-inch incision in the abdomen—the procedure Farney used to remove Dimitris’s grandfather’s kidney. Dimitris now has a functioning kidney; however, he must take anti-rejection medication for the rest of his life, Farney said. "He has a different life, but he’s happy to be able to eat foods he couldn’t have before because of his kidney condition." What was the first forbidden food Dimitris wanted after his transplant? Chocolate, of course. Kurt Samson is a freelance writer in Annapolis, Md.